Liposomes are used in a wide variety of medical applications, in which a chemical compound (“delivery compound”) is encapsulated in a liposome. Examples of delivery compounds include, but are not limited to, drugs, quantum dots, salts, nutrients, therapeutic agents, proteins, and contrast agents for use in enhanced magnetic resonance imaging and in model systems for the study of biological membranes.
It is desirable to control several aspects of liposome production efficiently: (1) the size of liposomes; (2) the amount of delivery compound encapsulated in each liposome; and (3) the amount of waste of a delivery compound (“loading efficiency”). Increased loading efficiency is particularly important for drug delivery applications as it reduces the amount of the delivery compound that is lost (discharged) during liposome production.
Reducing encapsulant waste through increased loading efficiency can dramatically drive down the commercial cost (and worldwide availability) of drug delivery and result in a profound commercial advantage among competing liposome formation processes. Loading efficiency is accomplished by controlling the stream of encapsulant introduced into a microfluidic device.
There are a number of methods and microfluidic device structures known in the prior art for producing liposomes. However, the size of the liposomes, the amount of delivery compound encapsulated, and the loading efficiency cannot be controlled by these processes. Moreover, processes known in the prior art require the use of costly secondary processes to manage liposome size differentials. The efficiency of some of these methods is often limited by their reliance on viscous shearing and emulsion processes which form liposomes under turbulent flow conditions which are not fully amenable to control.
For example, U.S. Pat. No. 7,595,195 (Lee '195) teaches the use of a microfluidic device for creating liposomes using an emulsion process.
The microfluidic device taught by Lee '195 is specifically used to create liposomes using controlled viscous shearing of oil-water emulsions under turbulent flow conditions (using immiscible fluids) to create liposomes.
Lee '195 teaches a device having a three channel structure. The three channel structure and method utilized by Lee '195 teaches introduction of encapsulent carried in a water stream into either the center channel or into the two outer channels.
The method disclosed by Lee '195, however, is unable to achieve formation of droplets smaller than 1 μm. For example, the process utilized by Lee '195 does not result in liposomes in the 100 to 300 nm range in a single process. Lee requires secondary processes to manage size differentials in the liposome population, including but not limited to sonication and membrane extrusion.
The size of liposomes is critical to the accurate delivery of drugs and other delivery compounds, therapeutic efficiency, and cellular uptake.
It is desirable to have a microfluidic apparatus and method for creating liposomes which (1) does not rely on the use of viscous shearing (turbulent flow) to produce liposomes; (2) does not require significant post-assembly and post-processing to create homogenous liposome populations; (3) can produce liposomes on a nanometer scale; and (4) can minimize the rate of discharge of the costly encapsulation compound.